Genetic counseling: 1p36 Deletion Syndrome-1
1p36 Deletion Syndrome Introduction *Introduce myself and acknowledge that I will be involved in their visit today. *Let them know that Counselor1 and Dr. Doktour will also be visiting with them today. *Small talk while walking to the room. *"What are your main concerns or questions that you would like addressed today?" Interim History *Explain that all of their concerns will be addressed later in the session, but that I would like to update the medical and developmental history from her last visit in February. *Who is her pediatrician? Any other physicians? *Any serious illnesses, hospitalizations or surgeries since February? *Current Medications? *Immunizations up to date? Review of Systems *Any diet or feeding concerns? *Any changes in skin pigmentation or birth marks? *Any heart concerns? (cardiologist found none) *Any bladder problems? *Any concerns about her hearing? Ear infections? PE tubes? *Any concerns with her behavior or sleep? *Any bowel problems? Constipation? *Any allergies? *Any concerns about vision or eyes? *Any concerns about seizures? Starring spells or repetitive behaviors? *Any other medical concerns (difficulty breathing) Developmental Assessment *Language **How many words does she have in her vocabulary? **Is she learning to sign? How many signs does she know? **Does she combine words into two word sentences? **Does she follow one or two step commands? **Can she point to any body parts? **How well is she able to indicate her wants? *Gross Motor **Is she standing independently? **Is she cruising? **Is she walking? Up stairs? *Visual Motor **How well does she hold and manipulate a crayon? **Drink from a cup? **Uses a spoon to feed? Started using a fork? **Can she help undress or dress herself? *Social **Imitates housework? **Behavior? (Rocking) *How do you feel her development compares with other children? *Do you feel she is making progress? Early Intervention *Ask about OT, PT and speech therapy. *How often? *Where is she receiving services? *What are they working on and what are the goals? *Is insurance covering these costs? *How do you think she is progressing? Psychosocial Assessment *Are all your other children living at home? *Things must be really hectic attending all her appointments and services on top of having ____ other children at home. How does it all work out? *Do you have help from other family members or others? *Do you have contact with any other families with 1p36 deletion syndrome? Etiology of 1p36 deletion syndrome (monosomy 1p36) *Caused by deletion of the most distal band of the short arm of chromosome1. *Most clinical manifestations are probably caused by the absence of one copy of a dose-sensitive gene and it is not possible to replace missing genes from chromosomes at this time. *Prevalence of this deletion is estimated to be 1 in 10,000 to as high as 1 in 5,000 (making it the most common terminal deletion) *Most cases result from sporadic deletions and are not inherited *1p36 deletion syndrome is usually diagnosed through recognition of the symptoms and characteristics as well as lab testing. This is done using high resolution chromosome analysis, or FISH with a chromosome 1-specific subtelomeric probe. The deletion often doesn't show up clearly with standard cytogenetic banding techniques. (In one group studied, about half were missed with chromosome analysis) *Patients with a 1p36 deletion have different sized pieces of the chromosome missing and may result in phenotype variability *Severity of associated disorders varies, but the physical features are very similar *Degree of MR and ability to acquire complex speech is somewhat dependent on deletion size *Most deletions affect the chromosome inherited from the mother (68%), but there doesn't seem to be differences in the clinical manifestations based on whether the deletion is on the paternal or maternal chromosome. *Those with paternally derived deletions tend to have larger deletions than those with maternally derived deletions *Mechanism causing chromosome breakage is unknown Characteristics *Children with 1p36 deletion syndrome are all unique individuals, but do have some common characteristics. *Distinct facial features including: small and pointed chin, flat nasal bridge, low-set ears, ear asymmetry, thickened ear helices, small head, deep-set eyes, large anterior fontanel, clinodactyly and/or short fifth finger *Most patients have mental retardation *Most patients have delayed growth and/or difficulty gaining weight. Some have difficulty with sucking and swallowing while others may not grow well even though they eat well. Some older children may become obese. *Most young children with 1p36 deletion syndrome have delayed development. *They sit up, walk and talk later than typical children. *Speech is severely affected with many patients learning only a few words *Other medical problems: hypotony (which may explain delayed motor skills), hearing loss, seizures, eye/vision problems, hypothyroidism, increased risk for neuroblastoma, heart defects (which have included cardiomyopathy, ductus arteriosus, tetralogy of Fallot, VSD), and orofacial clefting abnormalities, Recurrence Risk for next pregnancy *The majority of patients with 1p36 deletion syndrome are isolated cases resulting from a de novo deletion. There have been reports of patients with 1p36 deletion syndrome whose parents have a balanced translocation. *Parents should be tested for chromosomal rearrangements because about 6% of parents with an affected child have a balanced translocation *Translocation increases the chances of having another child with a 1p36 deletion. **If no translocation is found the chances of having another child with a 1p36 deletion are very small Prenatal Diagnosis *In 1999 a case was reported in which a 1p36 deletion in a fetus was detected when an amniocentesis was performed due to detection of multiple malformations on ultrasound *Another case was picked up prenatally because of the presence of elevated maternal serum alpha-fetoprotein (no abnormal sign seen on ultrasound). *Another was diagnosed prenatally because the mother was known to have a balanced translocation between the short arms of chromosome 1 and 20 that was picked up after their first child had inherited an unbalanced product. (no abnormal sign seen on ultrasound) Medical Treatment *Seizures can usually be controlled with medication *Medical interventions and feeding therapy may be needed to manage feeding issues *Early Intervention for developmental delay *Surgery may be necessary to correct heart defects, cleft lip, cleft palate if present *A urine screen for neuroblastoma should be performed every 6 months *Physical examinations should involve palpating the abdomen for lumps which might be neuroblastomas *There are no clear indications on whether they should continue to be followed by a cardiologist or whether the cardiomyopathy is limited to a congenital form. Psychosocial Issues *Initially parents may experience denial about how severe the developmental delay and mental retardation will be *Blaming of self or partner may occur *Stress of having a child with developmental delays and mental retardation *Stress associated with having a child with serious medical problems especially if they have heart malformations or seizures *Fear that the child might develop a neuroblastoma or seizures *Time commitment involved with early intervention services (OT, PT, speech therapy) Patient Resources *Chromosome Deletion Outreach http://www.chromosomedisorder.org *MUMS http://www.netnet.net/mums/ References *Shaffer, L.G. and Heilstedt, H.A. Terminal Deletion of 1p36. The Lancet Supplement December 2001; 358:89. *Faivre, L. et al. (1999) Prenatal Detection of a 1p36 Deletion in a Fetus with Multiple Malformations and a Review of the Literature. Prenatal Diagnosis. 19:49-53 *Heilstedt, H.A. et al. (2001) Loss of the Potassium Channel B-subunit gene, KCNAB2, Is Associated with Epilepsy in Patients with 1p36 Deletion Syndrome. Epilepsia. 42(9):1103-1111. *1p36 patient literature by Counselor1 that is currently in the process of being completed Notes The information for this outline was last updated in 2002. Material obtained under GFDL Licence from http://en.wikibooks.org/wiki/Handbook_of_Genetic_Counseling